dose escalation study of a pd1-lag3 bispecific antibody in patients with advanced and/or metastatic solid tumors

Conditions: Solid Tumors; Metastatic Melanoma; Non-small Cell Lung Cancer; Esophageal Squamous Cell Carcinoma

Summary: this is a first-in-human, open-label, multicenter, phase i multiple-ascending dose (mad) study of ro7247669, an anti pd-1 (programmed death-1) and lag-3 (lymphocyte-activation gene 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. this study aims to establish the maximum tolerated dose (mtd) and/or define the recommended phase 2 dose (rp2d) based on the safety, tolerability, pharmacokinetic (pk) and/or pharmacodynamic (pd) profile of ro7247669, and to evaluate preliminary anti-tumor activity in participants with solid tumors. an expansion part of the study is planned to enroll tumor-specific cohorts to evaluate anti-tumor activity of the mtd and/or rp2d of ro7247669 and to confirm safety and tolerability in participants with selected tumor types.


Eligibility criteria:
inclusion criteria * patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient * eastern cooperative oncology group performance status 0-1 * fresh biopsies may be required * women of childbearing potential and male participants must agree to remain abstinent or use contraceptive methods as defined by the protocol additional specific inclusion criteria for participants with melanoma * histologically confirmed, unresectable stage iii or stage iv melanoma * not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling in the study * prior treatment with an approved anti-pd-1 or anti-pd-l1 agent additional specific inclusion criteria for participants with non-small cell lung cancer who previously received treatment for metastatic disease * participants with histologically confirmed advanced non-small cell lung cancer * not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling in the study * previously treated with approved pd-l1/pd-1 inhibitors * tumor pd-l1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening additional specific inclusion criteria for participants with esophageal squamous cell carcinoma * participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus * participants who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling in the study additional specific inclusion criteria for participants with non-small cell lung cancer who previously did not receive treatment for metastatic disease * participants with histologically confirmed advanced non-small cell lung cancer * tumor pd-l1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening exclusion criteria * pregnancy, lactation, or breastfeeding * known hypersensitivity to any of the components of ro7247669 * active or untreated central nervous system (cns) metastases * an active second malignancy * evidence of concomitant diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications * positive hiv, hepatitis b, or hepatitis c test result * known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection * vaccination with live vaccines within 28 days prior to cycle 1 day 1 * treatment with oral or iv antibiotics within 2 weeks prior to cycle 1 day 1 * active or history of autoimmune disease or immune deficiency * prior treatment with adoptive cell therapies, such as car-t therapies * concurrent therapy with any other investigational drug \< 28 days or 5 half-lives of the drug, whichever is shorter, prior to the first ro7247669 administration * regular immunosuppressive therapy * radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy * prior treatment with a lymphocyte activation gene-3 (lag-3) inhibitor additional specific exclusion criteria for participants with non-small cell lung cancer who previously received treatment for metastatic disease * participants with the following muations, rearrangements, translocations are not eligible: egfr, alk, ros1, brafv600e, and ntrk additional specific exclusion criteria for participants with esophageal squamous cell carcinoma * prior therapy with any immunomodulatory agents additional specific exclusion criteria for participants with non-small cell lung cancer who previously did not receive treatment for metastatic disease * prior therapy for metastatic disease is not permitted * neo-adjuvant anti-pd-1 or anti-pd-l1 therapy is not allowed